Compositions and methods for treatment of skin infections

ABSTRACT

A pharmaceutical composition for treating skin infections is described herein. A method using a pharmaceutical composition for treating skin infections is described herein. A pharmaceutical composition for treating skin infections may comprise, in 100 parts of the composition, 1-99 parts of a pharmaceutically acceptable excipient; 99-1 parts of a keratolytic; 99-1 parts ethyl pyruvate; and 99-1 parts povidone iodine. A method for treating skin infections may comprise topical application of a composition to an infected skin cell for a treatment period.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.16/128,219, filed on Sep. 11, 2018, which is a divisional of U.S. patentapplication Ser. No. 15/679,113, filed on Aug. 16, 2017, which is acontinuation of PCT/US2016/018441, filed on Feb. 18, 2016, which claimsthe benefit of U.S. Provisional Application No. 62/119,076, filed Feb.20, 2015, each of which is incorporated herein by reference in itsentirety.

SUMMARY OF THE INVENTION

One embodiment of the current disclosure is a pharmaceutical compositioncomprising: a unit dose of at least about 15 weight % of a keratolyticagent, wherein the weight % of the keratolytic agent is based on a totalweight % of the composition, a molecule comprising an oxo group and anacidic group, ester thereof, salt thereof, or any combination thereof,and a halogen containing moiety. In some embodiments, the compositioncomprises at least about 18 weight % of salicylic acid, ester thereof,salt thereof, or any combination thereof, wherein the weight % ofsalicylic acid is based on the total weight % of the composition.

One embodiment of the current disclosure is a method of treatment of askin infection comprising administering to a subject in need thereof atherapeutically-effective amount of a pharmaceutical compositioncomprising: a unit dose of at least about 18 weight % of a keratolyticagent, wherein the weight % of the keratolytic agent is based on a totalweight % of the composition, a molecule comprising an oxo group and anacidic group, ester thereof, salt thereof, or any combination thereof,and a halogen containing moiety.

One embodiment of the current disclosure is a pharmaceuticalcomposition, comprising: a weight % of salicylic acid, ester thereof,salt thereof, or any combination thereof, from about 25% to about 30%,wherein the weight % of salicylic acid is based on a total weight % ofthe composition, a weight % of ethyl pyruvate, ester thereof, saltthereof, or any combination thereof, from about 10% to about 20%,wherein the weight % of ethyl pyruvate is based on a total weight % ofthe composition, and a weight % of polyvinylpyrrolidone-iodine fromabout 0.1% to about 1%, wherein the weight % ofpolyvinylpyrrolidone-iodine is based on a total weight % of thecomposition.

One embodiment of the current disclosure is a method of making apharmaceutical composition, comprising combining: a weight % ofsalicylic acid, ester thereof, salt thereof, or any combination thereof,from about 25% to about 30%, wherein the weight % of salicylic acid isbased on a total weight % of the composition, a molecule comprising anoxo group and an acidic group, ester thereof, salt thereof, or anycombination thereof, and a halogen containing moiety.

One embodiment of the current disclosure is a method of preventing acancer initiated by a virus comprising applying a compositioncomprising: a unit dose of at least about 18 weight % of a keratolyticagent, wherein the weight % of the keratolytic agent is based on a totalweight % of the composition, a molecule comprising an oxo group and anacidic group, ester thereof, salt thereof, or any combination thereof,and a halogen containing moiety.

One embodiment of the current disclosure is a method for treatment of awart comprising administering to a subject in need thereof atherapeutically-effective amount of a composition comprising: a weight %of salicylic acid, ester thereof, salt thereof, or any combinationthereof, from about 25% to about 30%, wherein the weight % of salicylicacid is based on a total weight % of the composition, a weight % ofethyl pyruvate, ester thereof, salt thereof, or any combination thereof,from about 10% to about 20%, wherein the weight % of ethyl pyruvate isbased on a total weight % of the composition, and a weight % ofpolyvinylpyrrolidone-iodine from about 0.1% to about 1%, wherein theweight % of polyvinylpyrrolidone-iodine is based on a total weight % ofthe composition.

One aspect of the present disclosure provides a composition for treatingskin infections, comprising: in 100 parts of the composition, 1-99 partsof a pharmaceutically acceptable excipient; 99-1 parts of a keratolytic;99-1 parts ethyl pyruvate; and 99-1 parts povidone iodine.

One aspect of the present disclosure provides a method for treating skininfections, comprising: topically applying a composition, comprising: in100 parts of a composition, 1-99 parts of a pharmaceutically acceptableexcipient; 99-1 parts of a keratolytic; 99-1 parts ethyl pyruvate; and99-1 parts povidone iodine, at ambient temperature, without usingcryotherapy, to an infection of the skin, resulting in a higher curerate than would be achieved if the infection were treated by topicallyapplying a control composition having only the keratolytic and balancebeing the pharmaceutically acceptable excipient.

One embodiment of the current disclosure is a pharmaceutically effectivecomposition for treatment of skin infections, comprising: in 100 partsof the composition, 1-99 parts of a pharmaceutically acceptableexcipient; 99-1 parts of a keratolytic; 99-1 parts ethyl pyruvate; and99-1 parts povidone iodine. In some aspects, the composition comprises:in 100 parts of the composition, 0-99 parts of a pharmaceuticallyacceptable excipient, 49.9-10 parts of a keratolytic, 50-5 parts ethylpyruvate, and 19-0.1 parts povidone iodine. In some aspects, thecomposition comprises: in 100 parts of the composition, 0-99 parts of apharmaceutically acceptable excipient, 0.4 parts to about 0.6 partspovidone iodine USP, 12.0 parts to about 18.0 parts ethyl pyruvate, and13.6 parts to about 20.4 parts salicylic acid USP. In some aspects, thecomposition comprises: in 100 parts of the composition, 0-99 parts of apharmaceutically acceptable excipient, 0.4 parts to about 0.6 partspovidone iodine USP, 12.0 parts to about 18.0 parts ethyl pyruvate, and19.2 parts to about 28.8 parts salicylic acid USP. In some aspects, thepharmaceutically acceptable excipient includes a thickening agent,wherein the thickening agent is selected from the group consisting ofnitrocellulose and hydroxypropyl Cellulose NF. In some aspects, thekeratolytic is selected from the group consisting of salicylic acid,pyruvic acid, chloroacetic acid, menthol, acetic acid, ascorbic acid,calcium pantothenate and lactic acid. In some aspects, the excipient isselected from the group consisting of polyethylene (PEG), ethyleneglycol (EG), polypropylene glycol (PPG), propylene glycol (PG) anddiethylene glycol monosubstituted ether (DGMSE). In some aspects, theexcipient is selected from the group consisting of BHT, glycerin,propylene glycol, transcutol, triethanolamine, hydroxypropyl cellulose,and combinations thereof. In some aspects, the skin infection is causedby human papillomavirus (HPV). In some aspects, the skin infection iswarts (verrucae) or squamous cell papilloma. In some aspects, the skininfection is cancer. In some aspects, the cancer is selected from thegroup consisting of cancer of the cervix, cancer of the vulva, cancer ofthe vagina, cancer of the penis, cancer of the oropharynx and cancer ofthe anus.

One embodiment of the current disclosure is a method for treating skininfections, comprising: topically applying the pharmaceuticallyeffective composition of claim 1 at ambient temperature to an infectionof the skin for treatment period prescribed by a physician, resulting ina higher cure rate than would be achieved if the infection were treatedby topically applying a control composition having only the keratolyticand balance being the pharmaceutically acceptable excipient. In someaspects, the keratolytic is selected from the group consisting ofsalicylic acid, pyruvic acid, chloroacetic acid, menthol, acetic acid,ascorbic acid, calcium pantothenate and lactic acid. In some aspects,the excipient is selected from the group consisting of polyethyleneglycol (PEG), ethylene glycol (EG), polypropylene glycol (PPG),propylene glycol (PG) and diethylene glycol monosubstituted ether(DGMSE). In some aspects, the excipient is selected from the groupconsisting of BHT, glycerin, propylene glycol, transcutol,triethanolamine, hydroxypropyl cellulose, and combinations thereof. Insome aspects, the skin infection is caused by Human papillomavirus(HPV). In some aspects, the skin infection is warts (verrucae) orsquamous cell papilloma. In some aspects, the skin infection is cancer.In some aspects, the cancer is selected from the group consisting ofcancer of the cervix, cancer of the vulva, cancer of the vagina, cancerof the penis, cancer of the oropharynx and cancer of the anus.

While preferred embodiments of the present disclosure are shown anddescribed herein, it is not meant to limit the present disclosure in anyfashion. The methods described herein are presently representative ofpreferred embodiments and are exemplary, and are not intended aslimitations on the scope of the disclosure. Changes therein and otheruses which are encompassed within the spirit of the disclosure asdefined by the scope of the claims will occur to those skilled in theart.

BACKGROUND OF THE INVENTION

The present disclosure relates to compositions and methods of treatmentof skin infection caused by Human papillomavirus (HPV). Specifically,the present disclosure relates to compositions and methods of treatingbenign papillomas, such as skin warts or squamous cell papilloma, orcancer, such as cancer of the cervix, cancer of the vulva, cancer of thevagina, cancer of the penis, cancer of the oropharynx and cancer of theanus.

A meta-analysis of topical treatment for cutaneous warts found a curerate of 23% (5-73%) in placebo trials, 52% (0-87%) in salicylic acidtrials, 49% (0-69%) in cryotherapy trials, 54% (45-75%) in aggressivecryotherapy trials and 58% (38-78%) in the combined cryotherapy andsalicylic acid trials. There continues to be a need for improvedcompositions and methods for treating skin infection caused by Humanpapillomavirus (HPV).

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the disclosure are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present disclosure will be obtained by reference tothe following detailed description that sets forth illustrativeembodiments, in which the principles of the disclosure are utilized, andthe accompanying drawings of which:

FIG. 1 depicts a flow diagram of a method for treating an infectioncaused by HPV, in accordance to embodiments of the present disclosure.

FIG. 2 depicts a chart illustrating results from topical treatment ofresistant wart patients in accordance with embodiments of the presentdisclosure.

FIG. 3 illustrates an example of a computer system that can be used inconnection with embodiments of the present disclosure.

DETAILED DESCRIPTION OF THE INVENTION

Pharmaceutical Compositions

The term “salt” refers to salts derived from a variety of organic andinorganic counter ions well known in the art. Acid addition salts can beformed with inorganic acids and organic acids. Inorganic acids fromwhich salts can be derived include, for example, hydrochloric acid,hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and thelike. Organic acids from which salts can be derived include, forexample, acetic acid, propionic acid, glycolic acid, pyruvic acid,oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid,tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid,methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid,salicylic acid, and the like. Base addition salts can be formed withinorganic and organic bases. Inorganic bases from which salts can bederived include, for example, sodium, potassium, lithium, ammonium,calcium, magnesium, iron, zinc, copper, manganese, aluminum, and thelike. Organic bases from which salts can be derived include, forexample, primary, secondary, and tertiary amines, substituted aminesincluding naturally occurring substituted amines, cyclic amines, basicion exchange resins, and the like, specifically such as isopropylamine,trimethylamine, diethylamine, triethylamine, tripropylamine, andethanolamine. In some embodiments, the base addition salt is chosen fromammonium, potassium, sodium, calcium, and magnesium salts.

The term “subject” includes, but is not limited to, humans of any agegroup, e.g., a pediatric subject (e.g., infant, child or adolescent) oradult subject (e.g., young adult, middle-aged adult or senior adult)and/or other primates (e.g., cynomolgus monkeys or rhesus monkeys);mammals, including commercially relevant mammals such as cattle, pigs,horses, sheep, goats, cats, and/or dogs; and/or birds, includingcommercially relevant birds such as chickens, ducks, geese, quail,and/or turkeys. The methods described herein can be useful in both humantherapeutics and veterinary applications. In some embodiments, thepatient is a mammal, and in some embodiments, the patient is human. Insome embodiments, a composition of the current disclosure isadministered to a subject in need thereof.

In some embodiments, a composition of the current disclosure isadministered to an infected cell. In some embodiments, a composition ofthe current disclosure is administered to an infected skin cell.

The term “therapeutically-effective amount” refers to that amount ofcompound that is sufficient to effect treatment, when administered to amammal in need of such treatment. The therapeutically-effective amountwill vary depending upon the subject and disease condition beingtreated, the weight and age of the subject, the severity of the diseasecondition, the manner of administration and the like, which can readilybe determined by one of ordinary skill in the art.

The compounds of the disclosure, or their pharmaceutically acceptablesalts, may contain one or more asymmetric centers and may thus give riseto enantiomers, diastereomers, and other stereoisomeric forms that aredefined, in terms of absolute stereochemistry, as (R)- or (S)- or, as(D)- or (L)- for amino acids. The present disclosure is meant to includeall such possible isomers, as well as their racemic and optically pureforms.

The term “pharmaceutically acceptable excipient” includes solvents,dispersion media, coatings, antibacterial and antifungal agents,isotonic and absorption delaying agents. Except insofar as anyconventional media or agent is incompatible with the active ingredient,its use in the therapeutic compositions of the disclosure iscontemplated. Supplementary active ingredients can also be incorporatedinto the compositions.

The term “treating” or “treatment” may include preventing adisease-state from occurring in a mammal, inhibiting a disease state,and relieving the disease state. Treating also may include theamelioration of a symptom of a disease (e.g., lessen the pain ordiscomfort), wherein such amelioration may or may not be directlyaffecting the disease (e cause, transmission, expression, etc.).

As used herein, unless otherwise defined, the term “resistant warts” or“resistant warts patients” refers to warts or patients with warts thatdo not clear readily. For example, a wart may not clear when topicallytreated with a composition.

As used herein, unless otherwise defined, the term “cure” may mean beingfree of a medical condition. A “cure rate” may mean no visible symptomsfor non-cancer diseases, as a percent of the originally infectedpopulation. “Cure” for cancer may be defined as being symptom free formore than 5 years.

The term “plantar wart” may also be known as verruca, myrmecia andverruca plantaris. Treatment for plantar warts may be recommended tolessen symptoms (which may include pain), decrease duration, and reducetransmission.

As used herein, unless otherwise defined, the term “pharmaceuticallyacceptable” refers to those properties and/or substances that areacceptable to the patient from a pharmacological/toxicological point ofview and to the manufacturing pharmaceutical chemist from aphysical/chemical point of view regarding composition, formulation,stability, patient acceptance, and bioavailability.

As used herein, unless otherwise defined, the term “pharmaceuticallyacceptable” refers to those properties and/or substances that areacceptable to the patient from a pharmacological/toxicological point ofview and to the manufacturing pharmaceutical chemist from aphysical/chemical point of view regarding composition, formulation,stability, patient acceptance, and bioavailability.

As used herein, unless otherwise defined, the terms “pharmaceuticallyeffective amount”, “pharmaceutically effective dose” or“pharmaceutically effective relief” is defined as an amount or dose thatresults in eradication of the wart, so that may not detectable by aphysician.

A therapeutically effective dose is an amount or dose that is effectivefor treating or preventing the disease or condition.

A composition of the current disclosure may comprise a keratolyticagent. In some embodiments, a keratolytic agent causes softening,shedding, or the combination thereof, of the outer layer of the skin. Akeratolytic agent may be a peeling agent. In some embodiments, akeratolytic agent can be salicylic acid, pyruvic acid, chloroaceticacid, menthol, acetic acid, ascorbic acid, calcium pantothenate orlactic acid. In some embodiments, a keratolytic agent of a compositionof the current disclosure is salicylic acid.

A composition of the current disclosure may comprise a moleculecomprising an oxo group and an acidic group, or ester or salt thereof. Acomposition may comprise a molecule comprising an oxo group and anacidic group, wherein the molecule comprises a pyruvate group. Acomposition of may comprise a molecule comprising an oxo group and anacidic group, wherein the molecule can be methyl pyruvate, ethylpyruvate, propyl pyruvate, or pyruvic acid. A composition of the currentdisclosure may comprise a molecule comprising an oxo group and an acidicgroup, wherein the molecule is ethyl pyruvate.

A composition of the current disclosure may comprise a halogencontaining moiety. A composition may comprise fluorine, bromine, iodine,chlorine, or combinations thereof. A composition may comprise iodine. Acomposition may comprise a cation, wherein the cation can be selectedfrom the group consisting of hydrogen cation, ammonium cation, andpolyvinylpyrrolidone cation. A composition of the current disclosure maycomprise polyvinylpyrrolidone-iodine.

In some embodiments, the amount of a compound in a composition can beexpressed by weight %, wherein the weight % of the compound is based ona total weight % of the composition.

In some embodiments, a compound can be present in a composition in about0.1 weight %, 0.2 weight %, 0.3 weight %, 0.4 weight %, 0.5 weight %,0.6 weight %, 0.7 weight %, 0.8 weight %, 0.9 weight %, 1 weight %, 2weight %, 3 weight %, 4 weight %, 5 weight %, 6 weight %, 7 weight %, 8weight %, 9 weight %, 10 weight %, 11 weight %, 12 weight %, 13 weight%, 14 weight %, 15 weight %, 16 weight %, 17 weight %, 18 weight %, 19weight %, 20 weight %, 21 weight %, 22 weight %, 23 weight %, 24 weight%, 25 weight %, 26 weight %, 27 weight %, 28 weight %, 29 weight %, 30weight %, 35 weight %, 40 weight %, 50 weight %, 60 weight %, 70 weight%, 80 weight %, 90 weight %, or 95 weight %, wherein the weight % of thecompound is based on a total weight % of the composition. In someembodiments, a compound is present in a composition in greater thanabout 0.1 weight %, 0.2 weight %, 0.3 weight %, 0.4 weight %, 0.5 weight%, 0.6 weight %, 0.7 weight %, 0.8 weight %, 0.9 weight %, 1 weight %, 2weight %, 3 weight %, 4 weight %, 5 weight %, 6 weight %, 7 weight %, 8weight %, 9 weight %, 10 weight %, 11 weight %, 12 weight %, 13 weight%, 14 weight %, 15 weight %, 16 weight %, 17 weight %, 18 weight %, 19weight %, 20 weight %, 21 weight %, 22 weight %, 23 weight %, 24 weight%, 25 weight %, 26 weight %, 27 weight %, 28 weight %, 29 weight %, 30weight %, 35 weight %, 40 weight %, 50 weight %, 60 weight %, 70 weight%, 80 weight %, 90 weight %, or 95 weight %, wherein the weight % of thecompound is based on a total weight % of the composition.

In some embodiments, a compound is present in a composition in apositive amount and less than about 0.1 weight %, 0.2 weight %, 0.3weight %, 0.4 weight %, 0.5 weight %, 0.6 weight %, 0.7 weight %, 0.8weight %, 0.9 weight %, 1 weight %, 2 weight %, 3 weight %, 4 weight %,5 weight %, 6 weight %, 7 weight %, 8 weight %, 9 weight %, 10 weight %,11 weight %, 12 weight %, 13 weight %, 14 weight %, 15 weight %, 16weight %, 17 weight %, 18 weight %, 19 weight %, 20 weight %, 21 weight%, 22 weight %, 23 weight %, 24 weight %, 25 weight %, 26 weight %, 27weight %, 28 weight %, 29 weight %, 30 weight %, 35 weight %, 40 weight%, 50 weight %, 60 weight %, 70 weight %, 80 weight %, 90 weight %, or95 weight %, wherein the weight % of the compound is based on a totalweight % of the composition.

In some embodiments, the amount of a keratolytic agent in a compositionis expressed by weight %, wherein the weight % of the keratolytic agentis based on a total weight % of the composition. In some embodiments,the amount of a keratolytic agent in a composition is greater than about18 weight %, 19 weight %, 20 weight %, 21 weight %, 22 weight %, 23weight %, 24 weight %, 25 weight %, 26 weight %, 27 weight %, 28 weight%, 29 weight %, 30 weight %, 35 weight %, 40 weight %, or 50 weight %,wherein the weight % of the keratolytic agent is based on a total weight% of the composition. In some embodiments, the amount of a keratolyticagent in a composition is greater than about 18 weight %. In someembodiments, the amount of a keratolytic agent in a composition is fromabout 25 weight % to about 30 weight %. In some embodiments, the amountof a keratolytic agent in a composition is about 28 weight %. In someembodiments, a keratolytic agent is salicylic acid. In some embodiments,the amount of salicylic acid in a composition is greater than about 18weight %, wherein the weight % of salicylic is based on a total weight %of the composition. In some embodiments, the amount of salicylic acid ina composition is from about 25 weight % to about 30 weight %. In someembodiments, the amount of salicylic acid in a composition is about 28weight %.

In some embodiments, the amount of ethyl pyruvate in a composition isexpressed by weight %, wherein the weight % of the ethyl pyruvate isbased on a weight % of the composition. In some embodiments, the amountof a ethyl pyruvate in a composition is about 10 weight %, 11 weight %,12 weight %, 13 weight %, 14 weight %, 15 weight %, 16 weight %, 17weight %, 18 weight %, 19 weight %, or 20 weight %, wherein the weight %of the ethyl pyruvate is based on a weight % of the composition. In someembodiments, the amount of ethyl pyruvate in a composition is from about10 weight % to about 20 weight %. In some embodiments, the amount ofethyl pyruvate in a composition is about 12 weight %.

In some embodiments, the amount of polyvinylpyrrolidone-iodine in acomposition is expressed by weight %, wherein the weight % ofpolyvinylpyrrolidone-iodine is based on a weight % of the composition.In some embodiments, the amount of polyvinylpyrrolidone-iodine in acomposition is about 0.1 weight %, 0.2 weight %, 0.3 weight %, 0.4weight %, 0.5 weight %, 0.6 weight %, 0.7 weight %, 0.8 weight %, 0.9weight %, or 1 weight %, wherein the weight % ofpolyvinylpyrrolidone-iodine is based on a weight % of the composition.In some embodiments, the amount of polyvinylpyrrolidone-iodine in acomposition is from about 0.1 weight % to about 1 weight %. In someembodiments, the amount of polyvinylpyrrolidone-iodine in a compositionis about 0.5 weight %.

In some embodiments, the ratio of ethyl pyruvate to salicylic acid in acomposition is about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10,2:3, 2:5, 2:7, 2:9, 2:11, 2:13, 2:15, 2:17, 2:19, 3:5, 3:7, 3:8, 3:10,3:11, 3:13, 3:14, 3:16, 3:17, 3:19, 4:5, 4:7, 4:9, 4:11, 4:13, 4:15,4:17, 4:19, 5:6, 5:8, 5:9, 5:11, 5:12, 5:13, 5:14, 5:16, 5:17, 5:18,5:19, 6:7, 6:11, 6:13, 6:17, 6:19, 7:8, 7:9, 7:10, 7:11, 7:12, 7:13,7:15, 7:16, 7:18, 7:19, 8:9, 8:11, 8:13, 8:15, 8:17, 8:19, 9:10, 9:11,9:13, 9:14, 9:16, 9:17, 9:19, 10:11, 10:13, 10:17, 10:19, 11:12, 11:13,11:14, 11:15, 11:16, 11:17, 11:18, 11:19, 11:20, 12:13, 12:17, 12:19,13:14, 13:15, 13:16, 13:17, 13:18, 13:19, 13:20, 14:15, 14:17, 14:19,15:16, 15:17, 15:19, 16:17, 16:19, 17:18, 17:19, 17:20, 18:19, or 19:20,wherein the ratio is based on a ratio of weight % of ethyl pyruvate tosalicylic acid. In some embodiments, the ratio of ethyl pyruvate tosalicylic acid in a composition is about 1:1, 1:2, 1:3, 1:4, or 1:5,wherein the ratio is based on a ratio of weight % of ethyl pyruvate tosalicylic acid. In some embodiments, the ratio of ethyl pyruvate tosalicylic acid in a composition is about 1:1, wherein the ratio is basedon a ratio of weight % of ethyl pyruvate to salicylic acid.

In some embodiments, the ratio of polyvinylpyrrolidone-iodine tosalicylic acid in a composition is about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6,1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90,1:100, 1:120, or 1:150, wherein the ratio is based on a ratio of weight% of polyvinylpyrrolidone-iodine to salicylic acid. In some embodiments,the ratio of polyvinylpyrrolidone-iodine to salicylic acid in acomposition is about 1:90. In some embodiments, the ratio ofpolyvinylpyrrolidone-iodine to salicylic acid in a composition is about1:120.

In some embodiments, the ratio of polyvinylpyrrolidone-iodine to ethylpyruvate in a composition is about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7,1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100,1:120, or 1:150, wherein the ratio is based on a ratio of weight % ofpolyvinylpyrrolidone-iodine to ethyl pyruvate. In some embodiments, theratio of polyvinylpyrrolidone-iodine to ethyl pyruvate in a compositionis about 1:90, wherein the ratio is based on a ratio of weight %. Insome embodiments, the ratio of polyvinylpyrrolidone-iodine to ethylpyruvate in a composition is about 1:120, wherein the ratio is based ona ratio of weight %.

In some embodiments, the pharmaceutical composition administered to apatient is in a unit dose, wherein the unit dose is in an amount fromabout 0.0001 g-500 g, 0.001 g-250 g, 0.01 g-100 g, 0.1 g-50 g, or 1 g-10g. In some embodiments, the unit dose is about or more than about 0.0001g, 0.001 g, 0.01 g, 0.1, 0.5 g, 1 g, 2 g, 3 g, 4 g, 5 g, 6 g, 7 g, 8 g,9 g, 10 g, 15 g, 20 g, 25 g, 50 g, 100 g, 200 g, 250 g, 300 g, 350 g,400 g, 450 g, 500 g, or more. In some embodiments, the unit dose is anamount from about 0.001 g-100 g. In some embodiments, the unit dose isan amount from about 0.1 g-10 g. In some embodiments, the unit dose isan amount from about 0.1 g-5 g.

In some embodiments, the composition can be provided in one or more unitdoses. For example, the composition can be administered in 1, 2, 3, 4,5, 6, 7, 14, 30, 60, or more doses. Such amount can be administered eachday, for example in individual doses administered once, twice, or threeor more times a day. In some embodiments, a unit dose may beadministered once a day. In some embodiments, a unit dose may beadministered twice a day. However, dosages stated herein on a per daybasis should not be construed to require administration of the dailydose each and every day. For example, if one of the agents is providedin a suitably slow-release form, two or more daily dosage amounts can beadministered at a lower frequency, e.g., as a depot every second day toonce a month or even longer.

The unit doses can be administered simultaneously or sequentially. Thecomposition can be administered for an extended treatment period. Thetreatment period can be about 1 minute, 1 hour, 12 hours, 1 day, 2 days,3 days, 7 days, 14 days, 28 days, 1 month, 2 months, 3 months, 6 months,or 1 year. In some embodiments, the treatment period may be untilsymptoms recede. In some embodiments, the composition is administeredfor a period of at least 1 minute. In some embodiments, the compositionis administered for a period of at least 1 hour.

In some embodiments, a composition of the current disclosure isadministered at least once a day for a period of at least one week. Insome embodiments, a composition of the current disclosure isadministered at least twice a day for a period of at least one week. Insome embodiments, a composition of the current disclosure isadministered at least once a day for a period of at least one month.

In some embodiments, a composition of the current disclosure can becontacted with infected skin at least once a day for a period of atleast one week. In some embodiments, a composition of the currentdisclosure can be contacted with infected skin at least twice a day fora period of at least one week. In some embodiments, a composition of thecurrent disclosure can be contacted with infected skin at least once aday for a period of at least one month.

In some embodiments, the pharmaceutical composition administered to apatient comprises a keratolytic agent, wherein the keratolytic agent ispresent in an amount from about 0.001-100 g. In some embodiments, thepharmaceutical composition administered to a patient comprises akeratolytic agent, wherein the keratolytic agent is present in an amountfrom about 0.1-10 g. In some embodiments, a composition of the currentdisclosure can be administered, wherein the administration can beselected from the group consisting of contacting, applying,administering, lathering, rubbing, dispensing, dispersing, anddistributing.

In some embodiments, a therapeutically-effective amount of a compositionof the current disclosure can sufficiently provide any one or more ofthe therapeutic effects described herein. As an example, thetherapeutically-effective amount can be in the range of about0.0001-1000 mg/kg body weight, 0.001-500 mg/kg body weight, 0.01-100mg/kg body weight, 0.01-30 mg/kg body weight, 0.1-200 mg/kg body weight,3-200 mg/kg body weight, 5-500 mg/kg body weight, 10-100 mg/kg bodyweight, 10-1000 mg/kg body weight, 50-200 mg/kg body weight, 100-1000mg/kg body weight, 200-500 mg/kg body weight, 250-350 mg/kg body weight,or 300-600 mg/kg body weight of a composition of the current disclosure.In some embodiments, the therapeutic amount can be about or more thanabout 0.0001 mg/kg body weight, 0.001 mg/kg body weight, 0.0.1 mg/kgbody weight, 0.1 mg/kg body weight, 0.5 mg/kg body weight, 1 mg/kg bodyweight, 2 mg/kg body weight, 3 mg/kg body weight, 4 mg/kg body weight, 5mg/kg body weight, 6 mg/kg body weight, 7 mg/kg body weight, 8 mg/kgbody weight, 9 mg/kg body weight, 10 mg/kg body weight, 15 mg/kg bodyweight, 20 mg/kg body weight, 25 mg/kg body weight, 50 mg/kg bodyweight, 100 mg/kg body weight, 200 mg/kg body weight, 250 mg/kg bodyweight, 300 mg/kg body weight, 350 mg/kg body weight, 400 mg/kg bodyweight, 450 mg/kg body weight, 500 mg/kg body weight, 600 mg/kg bodyweight, 800 mg/kg body weight, 1000 mg/kg body weight, or more of acomposition of the current disclosure. In some embodiments, theeffective amount is at least about 0.001 mg/kg body weight of acomposition of the current disclosure. In some embodiments, theeffective amount is an amount between about 0.01-30 mg/kg body weight ofa composition of the current disclosure. In some embodiments, thetherapeutic amount can be an amount between about 30-150 mg/kg bodyweight of a composition of the current disclosure.

The amount of composition administered will be dependent on the mammalbeing treated, the severity of the disorder or condition, the rate ofadministration, the disposition of the compound and the discretion ofthe prescribing physician. However, an effective dosage may be in therange of about 0.001 to about 10,000 mg per kg body weight per day, insingle or divided doses. In some instances, dosage levels below thelower limit of the aforesaid range may be more than adequate, while inother cases still larger doses may be employed without causing anyharmful side effect, e.g., by dividing such larger doses into severalsmall doses for administration throughout the day.

The term “about” when referring to a number or a numerical range meansthat the number or numerical range referred to is an approximationwithin experimental variability (or within statistical experimentalerror), and thus the number or numerical range may vary from, forexample, 1% to 10% of the stated number or numerical range.

In some embodiments, the disclosure provides a method for administrationof a composition of the current disclosure to a subject in need thereof.In some embodiments, a pharmaceutical composition comprising a compoundof the current disclosure may be administered to a subject in needthereof.

Subjects may be monitored for therapeutic effectiveness using assays andmethods suitable for the condition being treated, which assays will befamiliar to those having ordinary skill in the art and are describedherein. Pharmacokinetics of a compound of the current disclosure that isadministered to a subject may be monitored by determining the level ofthe compound in a biological fluid, for example, in the blood, bloodfraction (e.g., serum), and/or in the urine, and/or other biologicalsample or biological tissue from the subject. Any method practiced inthe art and described herein to detect the compound may be used tomeasure the level of the compound during a treatment course.

In some embodiments, an infection can cause a symptom. Symptoms caninclude, but are not limited to, redness, tenderness, swelling, warmthof the infected area, a wart, a rash, a discolored patch of skin,scaling, cracking, soreness, maceration, pimples, pustules, lesions, orcombinations thereof. In some embodiments, a symptom can be a wart.

A composition of the current disclosure may be used to treat a symptomof a skin infection. In some embodiments, the method reduces thediameter of a wart by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%,70%, 80%, 90%, or more. In some embodiments, the method reduces thediameter of a wart by at least 50%. In some embodiments, the methodreduces the mass of a wart by at least about 5%, 10%, 20%, 30%, 40%,50%, 60%, 70%, 80%, 90%, or more. In some embodiments, the methodreduces the mass of a wart by at least 10%. In some embodiments, themethod reduces the volume of a wart by at least about 5%, 10%, 20%, 30%,40%, 50%, 60%, 70%, 80%, 90%, or more. In some embodiments, the methodreduces the volume of a wart by at least 10%. In some embodiments, amethod of the current disclosure is a method for treatment of a wartcomprising administering to a subject in need thereof atherapeutically-effective amount of a composition comprising: a weight %of salicylic acid, or a salt thereof, from about 25% to about 30%,wherein the weight % of salicylic acid is based on a weight % of thecomposition, a weight % of ethyl pyruvate, or a salt thereof, from about10% to about 20%, wherein the weight % of ethyl pyruvate is based on aweight % of the composition, and a weight % ofpolyvinylpyrrolidone-iodine from about 0.1% to about 1%, wherein theweight % of polyvinylpyrrolidone-iodine is based on a weight % of thecomposition.

A composition of the current disclosure may be used in a method, whereinthe method induces a lower amount of a symptom compared to othercompositions, wherein these other compositions comprise an ingredientselected from the group consisting of 5-fluorouracil,dinitrochlorobenzene, bleomycin, cantharidin, and any combinationthereof. A composition of the current disclosure may induce a loweramount of a symptom by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%,70%, 80%, 90%, or more. In some embodiments, a method of the currentdisclosure induces lower than about 50% of a symptom compared to amethod employing a composition comprising an ingredient selected fromthe group consisting of 5-fluorouracil, dinitrochlorobenzene, bleomycin,cantharidin, and any combination thereof.

A composition of the current disclosure may be used in a method, whereinthe method exhibits greater efficacy compared to other compositions,wherein these other compositions comprise an ingredient selected fromthe group consisting of 5-fluorouracil, dinitrochlorobenzene, bleomycin,cantharidin, and any combination thereof. A composition of the currentdisclosure may exhibit greater efficacy compared to other compositionsby at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, ormore. A composition of the current disclosure may exhibit greaterefficacy compared to other compositions by at least about 10%. Acomposition of the current disclosure may exhibit greater efficacycompared to other compositions by at least about 50%. A composition ofthe current disclosure may exhibit greater efficacy compared to othercompositions by at least about 75%.

A composition of the current disclosure may be used in a method to treatskin infections that are resistant to other methods that employcompositions that comprise an ingredient selected from the groupconsisting of 5-fluorouracil, dinitrochlorobenzene, bleomycin,cantharidin, and any combination thereof. In some embodiments, a subjecthad been previously diagnosed with a skin infection prior toadministration of a composition of the current disclosure.

Combination Therapy

In some embodiments, pharmaceutical compositions disclosed herein can beused in combination therapy with other therapeutic agents. Thepharmaceutical compositions disclosed herein and the therapeutic agentcan act additively or synergistically. In some embodiments,pharmaceutical compositions disclosed herein are administeredconcurrently with the administration of another therapeutic agent. Insome embodiments, pharmaceutical compositions disclosed herein areadministered prior or subsequent to administration of other therapeuticagents. Other therapeutic agents may include, but are not limited to,5-fluorouracil, dinitrochlorobenzene, bleomycin, cantharidin, or anycombination thereof.

In some embodiments, pharmaceutical compositions disclosed herein can beused in combination therapy with additional treatments. Thepharmaceutical compositions disclosed herein and the additionaltreatments can act additively or synergistically. In some embodiments,pharmaceutical compositions disclosed herein are administeredconcurrently with the additional treatments. In some embodiments,pharmaceutical compositions disclosed herein are administered prior orsubsequent to additional treatments. Additional treatments may include,but are not limited to, cryotherapy, electrosurgery, excision, lasertreatment, surgery, immunotherapy, or any combination thereof.

In some embodiments, pharmaceutical compositions disclosed herein can beused in combination therapy with an additional active agent. Theadditional active agent may be an antiviral drug, an anticancer drug, anantibacterial drug, or any combinations thereof. In some embodiments,the additional active agent is an antiviral drug. In some embodiments,the additional active agent is 5-fluorouracil, dinitrochlorobenzene,bleomycin, cantharidin, minocycline, doxycycline, tetracycline,erythromycin, metronidazole, sulfacetamide, clindamycin, sulfacetamide,or any combination thereof.

In one embodiment, the composition for treating skin infectionsadvantageously comprises in 100 parts of the composition, 0-99 parts ofa pharmaceutically acceptable excipient, 49.9-10 parts of a keratolytic,50-5 parts ethyl pyruvate, and 19-0.1 parts povidone iodine.

In one embodiment, the composition for treating skin infectionsadvantageously comprises in 100 parts of the composition, 0-99 parts ofa pharmaceutically acceptable excipient, 0.4 parts to about 0.6 partspovidone iodine USP, 12.0 parts to about 18.0 parts ethyl pyruvate, and19.2 parts to about 28.8 parts salicylic acid USP.

In some embodiments, the pharmaceutical composition of the currentdisclosure comprises an excipient. Some examples of excipients includestarches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin,calcium silicate, microcrystalline cellulose, PEG, nitrocellulose,hydroxypropyl Cellulose NF, polyvinylpyrrolidone, cellulose, water,sterile saline, syrup, and methyl cellulose, lubricating agents such astalc, magnesium stearate, and mineral oil, wetting agents, emulsifyingand suspending agents, preserving agents such as methyl- andpropylhydroxy-benzoates; sweetening agents, flavoring agents such aslactose, dextrose, sucrose, sorbitol, mannitol, and scented agents, suchas cinnamon, olive oil, menthol, saffron, citrus.

In some embodiments, the pharmaceutical composition of the currentdisclosure comprises an excipient, wherein the excipient is selectedfrom ethyl alcohol, camphor, castor oil, collodion, ethyl ether,ethylcullulose, hypophosphorous acid, menthol, and polysorbate 80.

In some embodiments, an excipient may be a thickening agent. In someembodiments, a composition of the current disclosure comprises athickening agent, wherein the thickening agent may be selected from thegroup consisting of polyethylene glycol, polyacrylic acid, vegetablegums, petroleum jelly, guar gum, sodium chloride, nitrocellulose,hydroxypropyl cellulose, and any combination thereof. In someembodiments, a thickening agent may be selected from the groupconsisting of nitrocellulose, hydroxypropyl cellulose, and anycombination thereof. In some embodiments, a thickening agent may benitrocellulose. In some embodiments, a thickening agent is hydroxypropylCellulose NF. In some embodiments, the excipient may be selected fromthe group consisting of water, polyethylene glycol, ethylene glycol,polypropylene glycol, propylene glycol, 2-(2-ethoxyethoxy)ethanol,butylated hydroxytoluene, glycerin, 2-(2-ethoxyethoxy)ethanol,triethanolamine, Vitamin E, mineral oil, and dimethyl sulfoxide,gelatin, calcium silicate, and hydroxypropyl cellulose. In someembodiments, the excipient may be polyethylene (PEG), ethylene glycol(EG), polypropylene glycol (PPG), propylene glycol (PG) or diethyleneglycol monosubstituted ether (DGMSE). In some embodiments, the excipientmay be glycerin, propylene glycol, transcutol, triethanolamine,hydroxypropyl cellulose, or combinations thereof. In some embodiments,the excipient may be polyethylene glycol, ethylene glycol, polypropyleneglycol, propylene glycol, or diethylene glycol monosubstituted ether. Apharmaceutically acceptable excipient may be used to promotesolubilization of the components of the pharmaceutically effectivecomposition.

Composition of the current disclosure may be formulated for rapid,sustained, delayed release, or combinations thereof.

FIG. 1 depicts a method 100 for treating skin infections. The method 100comprises a step 105: topically applying to an infection of the skin fortreatment period prescribed by a physician, at ambient temperature,without using cryotherapy, a composition for treating skin infections,comprising: in 100 parts of the composition, 1-99 parts of apharmaceutically acceptable excipient; 99-1 parts of a keratolytic; 99-1parts ethyl pyruvate; and 99-1 parts povidone iodine, resulting in ahigher cure rate than would be achieved if the infection were treated bytopically applying a control composition having only the keratolytic andbalance being the pharmaceutically acceptable excipient.

Ethyl alcohol may be used to dissolve components of the pharmaceuticallyeffective composition for treating infections caused by HPV. Alcohols,such as isopropyl alcohol, methyl alcohol, propyl alcohol, ethylalcohol, cetyl alcohol, stearyl alcohol, cetearyl alcohol, and lanolinalcohol, may be used for dissolving or taking up the components in thepharmaceutically effective composition for treating infections caused byHPV. Alternatively, for example, for topical formulations,pharmaceutically acceptable excipients may comprise solvents,emollients, humectants, preservatives, emulsifiers, and pH adjustingagents. Suitable solvents include acetone, glycols, polyurethanes, andothers known in the art. Suitable emollients include mineral oil,propylene glycol dicaprylate, lower fatty acid esters, lower alkylethers of propylene glycol, cetyl alcohol, cetostearyl alcohol, stearylalcohol, stearic acid, wax, and others known in the art. Suitablehumectants include glycerin, sorbitol, and others known in the art.Suitable emulsifiers include glyceryl monostearate, glyceryl monoleate,stearic acid, polyoxyethylene cetyl ether, polyoxyethylene cetostearylether, polyoxyethylene stearyl ether, polyethylene glycol stearate,propylene glycol stearate, and others known in the art. Suitable pHadjusting agents include hydrochloric acid, phosphoric acid,diethanolamine, triethanolamine, sodium hydroxide, monobasic sodiumphosphate, dibasic sodium phosphate, and others known in the art.Alternatively, pH adjusting agents include, from about 1 percent byweight to about 15 percent by weight, acetic acid, citric acid, pyruvicor lactic acid. Suitable preservatives include butylated hydroxytolueneNF, benzyl alcohol, sodium benzoate, parabens, and others known in theart.

Polyethylene glycol (PEG), ethylene glycol (EG), polypropylene glycol(PPG), propylene glycol (PG) and the diethylene glycol monosubstitutedether (DGMSE) can be pharmaceutically acceptable excipients. DGMSE maybe known as 2-(2-ethoxyethoxy)ethanol, Carbitol, Carbitolcellosolve,Transcutol, Dioxitol, Poly-solv DE, and Dowanol DE. Not wishing to bebound by theory, polyethylene glycol (PEG), ethylene glycol (EG),polypropylene glycol (PPG), propylene glycol (PG) and the diethyleneglycol monosubstituted ether (DGMSE) may hydrogen bond to tracenucleophiles that may be contaminants in the pharmaceutically acceptableexcipients, thereby reducing the nucleophilic strength of the tracenucleophiles. This may reduce the chance that ethyl pyruvate maydecompose by undergoing disadvantageous nucleophilic attack by the tracenucleophiles. Therefore diethylene glycol monosubstituted ether (DGMSE)or silicones such as dimethicone or cyclomethicone may be useful aspharmaceutically acceptable excipients.

In one embodiment, patients topically treated with the pharmaceuticallyeffective composition for treating infections caused by HPV compoundedinto a polypropylene glycol (PPG, molecular weight from about 300 toabout 2500), propylene glycol (PG,), polyethyleneglycol (PEG, molecularweight from about 100 to about 1000) or ethylene glycol ointment orcream showed very little evidence of any systemic toxicities.

Hydroxypropyl cellulose, hydroxyethyl cellulose and hydroxymethylcellulose are gelling and thickening agents derived from cellulose.Hydroxypropyl cellulose may be Hydroxypropylcellulose NF 1500 CPS. Itmay be used in cosmetics, cleaning solutions, and other householdproducts. Hydroxypropyl cellulose, hydroxyethyl cellulose andhydroxymethyl cellulose can be used to solubilize hydrophobic andhydrophilic components in a composition.

Formulations

When desired, the (R)- and (S)-isomers of the compounds of the presentdisclosure, if present, may be resolved by methods known to thoseskilled in the art, for example by formation of diastereoisomeric saltsor complexes which may be separated, for example, by crystallization;via formation of diasteroisomeric derivatives which may be separated,for example, by crystallization, gas-liquid or liquid chromatography;selective reaction of one enantiomer with an enantiomer-specificreagent, for example enzymatic oxidation or reduction, followed byseparation of the modified and unmodified enantiomers; or gas-liquid orliquid chromatography in a chiral environment, for example on a chiralsupport, such as silica with a bound chiral ligand or in the presence ofa chiral solvent. Alternatively, a specific enantiomer may besynthesized by asymmetric synthesis using optically active reagents,substrates, catalysts or solvents, or by converting one enantiomer tothe other by asymmetric transformation.

When employed as pharmaceuticals, the compounds described herein can beadministered in the form of pharmaceutical compositions. This disclosuretherefore provides pharmaceutical compositions which contain activeingredients or a pharmaceutically acceptable salt thereof and one ormore pharmaceutically acceptable excipients, carriers, diluents,permeation enhancers, solubilizers or adjuvants. Compositions of thecurrent disclosure may be administered alone or in combination withother therapeutic agents (e.g., vasoconstrictors, anti-inflammatoryagents, antibiotics, other monobinding anesthetic bases and salts,counter-irritants), carriers, adjuvants, permeation enhancers, and thelike. Pharmaceutically acceptable salts of the active agents (e.g., acidaddition salts) may be prepared using standard procedures known to thoseskilled in the art.

Compositions of the current disclosure may be administered by any of theaccepted modes of administration of agents having similar utilities, forexample, by oral, topical, intradermal, intravenous, subcutaneous,intramuscular, intra-articular, intraspinal or spinal, epidural, rectal,vaginal, or transdermal/transmucosal routes. The most suitable routewill depend on the nature and severity of the condition being treated.Subcutaneous, intradermal and percutaneous injections can be routes forthe compounds of this disclosure. In making the compositions of thisdisclosure, the active ingredient can be diluted by an excipient. Someexamples of suitable excipients include mannitol, starches, gum acacia,calcium phosphate, alginates, tragacanth, gelatin, calcium silicate,microcrystalline cellulose, PEG, polyvinylpyrrolidone, cellulose, water,sterile saline, syrup, and methyl cellulose. The formulations canadditionally include: lubricating agents such as talc, magnesiumstearate, and mineral oil; wetting agents; emulsifying and suspendingagents; preserving agents such as methyl- and propylhydroxy-benzoates;sweetening agents; and flavoring agents. The compositions of thedisclosure can be formulated so as to provide quick, sustained ordelayed release of the active ingredient after administration to thepatient by employing procedures known in the art.

A pharmaceutical composition (e.g., for oral administration or forinjection, infusion, subcutaneous delivery, intramuscular delivery,intraperitoneal delivery or other method) may be in the form of aliquid. A liquid pharmaceutical composition may include, for example,one or more of the following: a sterile diluent such as water, salinesolution, preferably physiological saline, Ringer's solution, isotonicsodium chloride, fixed oils that may serve as the solvent or suspendingmedium, polyethylene glycols, glycerin, propylene glycol or othersolvents; antibacterial agents; antioxidants; chelating agents; buffersand agents for the adjustment of tonicity such as sodium chloride ordextrose. A parenteral composition can be enclosed in ampoules,disposable syringes or multiple dose vials made of glass or plastic.Physiological saline may be used. Compositions of the current disclosuremay be sterile. In another embodiment, for treatment of anophthalmological condition or disease, a liquid pharmaceuticalcomposition may be applied to the eye in the form of eye drops. A liquidpharmaceutical composition may be delivered orally.

Compositions of the current disclosure can be in the form of emulsions,creams, jelly, solutions, ointments, or combinations thereof. Acomposition may be semisolid.

Compositions of the current disclosure can be administered topically tonon-ocular mucous membranes, such as for example oral, otic, nasal,respiratory, pharyngeal, tracheal, esophageal, urethral, or vaginalmembranes. Formulations containing at least one compound of thedisclosure useful for such membranes may be, for example, solutions,sprays, suspensions, gels, creams or ointments.

A composition of the current disclosure may be formulated into a topicalsolution, a lotion, a cream, an ointment, a gel, a foam, a patch, apowder, onto a sponge, a paste, a tincture, or any combination thereof.A composition of the current disclosure may be formulated into a cream,an ointment, or a gel. A composition of the current disclosure may beformulated into a gel. A composition of the current disclosure may behomogenous. A composition of the current disclosure may beheterogeneous.

Compatible and pharmaceutically acceptable carriers, which may be usedin this disclosure, comprise e.g. an aqueous solution, such as salinesolutions, oil solutions or ointments. Formulations for ocular use mayalso contain compatible and pharmaceutically acceptable excipients, suchas preservatives, surfactants, stabilizing agents, antibacterial agents,buffering agents and agents such as for example polymers to adjustviscosity, vasoconstrictors, antihistaminic agents or anti-inflammatoryagents. Formulations may be manufactured in different dosage units,suitable for ocular administration. The concentration of active compoundin a formulation for use on non-ocular mucous membranes can be fromabout 0.01% to 20% by weight.

Injectable solutions may contain a vasoconstrictor (e.g. epinephrine orvasopressin); a solution for infusion or regional anesthesia may containglucose or dextrose, a gel for urogenital topical procedures may containthickening agents (e.g. hydroxypropylmethylcellulose); a preparation fortopical or dermal application may contain penetration promoting agents(e.g. hydroxypolyethoxydodecane, DMSO, DMAC); sprays for topicalanesthesia of the mouth and oropharynx may contain saccharin andalcohol, ointments for accessible mucous membranes may contain alubricant. Compositions of the current disclosure can also beadministered together with other membrane stabilizers (localanesthetics), for example to form eutectic mixtures. The compositions ofthe disclosure can also be administered together with othertherapeutically active compounds, such as capsaicin, vaso-activecompounds, anti-inflammatory agents, or combinations thereof.

In some embodiments, the area of skin around an infected skin cell isprepared before administration of a composition of the currentdisclosure. Preparation of the area of skin around an infected skin cellmay include washing, drying, dressing with an absorbent material,dressing with an adhesive bandage, contacting with ice, contacting witha warm or hot cloth, or combinations thereof. In some embodiments, thearea of skin around an infected skin cell is washed and dried beforeadministration of a composition of the current disclosure. In someembodiments, an adhesive bandage is applied to an area of skin around aninfected skin cell.

For oral formulations, at least one of the compounds described hereincan be used alone or in combination with appropriate additives to maketablets, powders, granules or capsules, and if desired, with diluents,buffering agents, moistening agents, preservatives, coloring agents, andflavoring agents. The compounds may be formulated with a buffering agentto provide for protection of the compound from low pH of the gastricenvironment and/or an enteric coating. A compound included in apharmaceutical composition may be formulated for oral delivery with aflavoring agent, e.g., in a liquid, solid or semi-solid formulationand/or with an enteric coating.

A pharmaceutical composition may be formulated for sustained or slowrelease (also called timed release or controlled release). Suchcompositions may generally be prepared using known technology andadministered by, for example, oral, rectal, intradermal, or subcutaneousimplantation, or by implantation at the desired target site.Sustained-release formulations may contain the compound dispersed in acarrier matrix and/or contained within a reservoir surrounded by a ratecontrolling membrane. Excipients for use within such formulations may bebiocompatible, and may also be biodegradable. The formulation mayprovide a relatively constant level of active component release.Non-limiting examples of excipients include water, alcohol, glycerol,chitosan, alginate, chondroitin, Vitamin E, mineral oil, and dimethylsulfoxide. The amount of active compound contained within a sustainedrelease formulation depends upon the site of implantation, the rate andexpected duration of release, and the nature of the condition, diseaseor disorder to be treated or prevented.

Compositions of the current disclosure may be solubilized andencapsulated, for example, in a liposome or a biodegradable polymer, orused in the form of microcrystals coated with an appropriate nontoxiclipid.

The compositions may be formulated to provide for drug latentiation bythe conversion of hydrophilic drugs into lipid-soluble drugs.Latentiation may be achieved through blocking of the hydroxyl, carbonyl,sulfate, or primary amine groups present on a compound to render thecompound more lipid soluble and amenable to transportation across tissuebarriers.

Compositions of the disclosure may be formulated as a spray.Compositions may include solutions and suspensions in pharmaceuticallyacceptable, aqueous or organic solvents, or mixtures thereof, andpowders. The liquid or solid compositions may contain suitablepharmaceutically acceptable excipients as described supra.

Another formulation for use in the methods of the present disclosureemploys transdermal delivery devices (“patches”). Such transdermalpatches may be used to provide continuous or discontinuous infusion ofthe compounds of the present disclosure in controlled amounts. Suchpatches may be constructed for continuous, pulsatile, or on demanddelivery of pharmaceutical agents.

The compositions are preferably formulated in a unit dosage form. Theterm “unit dosage forms” refers to physically discrete units suitable asunitary dosages for human subjects and other mammals, each unitcontaining a predetermined quantity of active material calculated toproduce the desired therapeutic effect, in association with a suitablepharmaceutical excipient.

Compositions of the current disclosure can be formulated aspharmaceutical compositions which are suitable for intravenousadministration. For intravenous administration, the compositions can beformulated in aqueous media using water-immiscible solvents,solubilizers, emulsifiers, surfactants or other solubilizing agents.Individual formulations may include one or more additional componentssuch as stabilizers, tonicity modifiers, bases or acids to adjust pH,and solubilizers. The formulations can also optionally contain apreservative, such as ethylenediaminetetraacetic acid (EDTA) or sodiummetabisulfate, to prevent the growth of microorganisms.

Pharmaceutical formulations may include stabilizing agents, which can beconsidered as co-emulsifiers. Anionic stabilizers includephosphatidylethanolamines, conjugated with polyethylene glycol, (PEG-PE)and phosphatidylglycerols, a specific example of which isdimyristolphosphatidylgylcerol (DMPG). Additional examples of usefulstabilizers include oleic acid and its sodium salt, cholic acid anddeoxycholic acid and their respective salts, cationic lipids such asstearylamine and oleylamine, and3β-[N—(N,N′-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol).

A pharmaceutical composition of the disclosure can be made isotonic withblood by the incorporation of a suitable tonicity modifier. Apharmaceutical composition of the disclosure may have a pH of about 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14, as measured by, forexample, a pH probe or pH paper. A composition may have a pH from about4 to about 10. A pharmaceutical composition may be formulated to be atphysiologically neutral pH.

Solutions containing the compounds of the present disclosure may beadministered by injection or infusion, using suitable devices such asregular syringes or infusion devices, in the form of a pharmaceuticalpreparation which contains at least one compound of the disclosureeither as a free base or as a pharmaceutically acceptable, non-toxicacid addition salt, such as for example hydrochloride, lactate, acetate,sulfamate, in combination with a pharmaceutically acceptable carrier.

Compositions of the current disclosure may be formulated into solutionsfor injection or infusion or infiltration. These solutions may containstabilizing agents, antibacterial agents, buffering agents and may bemanufactured in different dosage unit ampoules, single-use syringes orbottles.

The compounds of the present disclosure, or their pharmaceuticallyacceptable salts, are administered in a therapeutically-effectiveamount. It will be understood, however, that the amount of the compoundactually administered will be determined by a physician or clinician, inthe light of the relevant circumstances, including the condition to betreated, the chosen route of administration, the compound administeredand its relative activity, the age, weight, and response of theindividual patient, the severity of the patient's symptoms, and thelike.

In some embodiments, a method of making a pharmaceutical composition,comprises combining a weight % of salicylic acid, or a salt thereof,from about 25% to about 30%, wherein the weight % of salicylic acid isbased on a weight % of the composition, a molecule comprising an oxogroup and an acidic group, or ester or salt thereof, and a halogencontaining moiety.

A compound of the present disclosure can be prepared by a methodwell-known to those skilled in the art. However, methods for preparingthe composition of the present disclosure are not limited to thosedescribed in the examples, and appropriate alterations and modificationscan be added to these methods.

Indications

Compositions of the current disclosure may be used to treat aninfection.

In some embodiments, a composition of the current disclosure is may beused to treat a skin infection. The skin infection may be caused by abacterium, a virus, or a fungus. Bacterial skin infections include, butare not limited to, leprosy, carbuncles, Staphylococcus aureusinfection, cellulitis, impetigo, boils, pilonidal cyst, abscess, orcombinations thereof. Fungal skin infections include, but are notlimited to, ringworm, athlete's foot, yeast infection, sporotrichosis,fungal nail infection, or combinations thereof.

In some embodiments, a composition of the current disclosure is used totreat a skin condition, wherein the skin conditions is rosacea. The skininfection may be caused by exposure to extreme temperatures, exercise,heat from sunlight, sunburns, stress, anxiety, cold wind, orcombinations thereof.

Viral skin infections include, but are not limited to, molluscumcontagiosum, shingles, chickenpox, herpes simplex virus, humanpapillomavirus, herpes zoster, molluscum contagiosum virus, humanherpesvirus-3, and varicella. In some embodiments, the skin infection iscaused by a virus. In some embodiments, the virus is selected from thegroup consisting of herpes simplex virus, human papillomavirus, herpeszoster, molluscum contagiosum virus, human herpesvirus-3, and varicella.In some embodiments, the skin infection is caused by the molluscumcontagiosum virus. In some embodiments, the skin infection is caused bythe human papillomavirus. In some embodiments, the skin infection is awart, verruca vulgaris, verrucae, Plantar's warts, or squamous cellpapilloma. In some embodiments, a composition of the current disclosureis used to treat a skin infection, wherein the skin infection is a wart.In some embodiments, the skin infection is benign or non-cancerous. Skininfections of the current disclosure may be contagious.

In some embodiments, the skin infection is cancerous. Skin infections ofthe current disclosure may be noncontagious. In some embodiments, theskin infection is cancer. In some embodiments, a composition of thecurrent disclosure is used to treat cancer. In some embodiments, theskin infection may be cancer of the cervix, cancer of the vulva, cancerof the vagina, cancer of the penis, cancer of the oropharynx or cancerof the anus. In some embodiments, the current disclosure provides amethod of preventing a cancer initiated by a virus, comprisingapplication a composition of the current disclosure to a cell infectedwith a virus.

In some embodiments, the composition of the current disclosure retainsgreater than 50% of a keratolytic agent after placement in a sealedcontainer for 6 months at a temperature of about 25° C. and a relativehumidity level of about 50%. In some embodiments, the composition of thecurrent disclosure retains at least 80% of the keratolytic agent afterplacement in a sealed container for 6 months at a temperature of about25° C. and a relative humidity level of about 50%.

A composition of the current disclosure may be packaged into a containerselected from the group consisting of a tube, a jar, a vial, a bag, atray, a drum, a bottle, a syringe, and a can. In some embodiments, acomposition of the current disclosure may be packaged into a tube. Insome embodiments, a composition of the current disclosure may bepackaged into a tube, wherein the tube contains information describingdirections for use. In some embodiments, a composition of the currentdisclosure may be packaged into a tube, wherein the tube containsinformation describing directions for use, wherein the directions foruse are for treating a wart.

Kits with unit doses of one or more of the compounds described hereinare provided. Such kits may include a container containing a unit dose,an informational package insert describing the use and attendantbenefits of the drugs in treating the disease, and optionally anappliance or device for delivery of the composition.

The kit may further comprise any device suitable for administration ofthe composition. For example, a kit comprising a topical formulation ofpharmaceutical compositions may comprise gel suitable for topicaladministration and an alcohol wipe for sterilization of the applicationsite.

In some cases, kits may be provided with instructions. The instructionsmay be provided in the kit or they may be accessed electronically (e.g.,on the World Wide Web). The instructions may provide information on howto use the compositions of the present disclosure. In some embodiments,the kit comprises instructions for use in treating a wart. Theinstructions may provide information on how to perform the methods ofthe disclosure. In some embodiments, the kit comprises instructions formethods of treating a wart. In some cases, the instructions may providedosing information. The instructions may provide drug information suchas the mechanism of action, the formulation of the drug, adverse risks,contraindications, and the like. In some cases, the kit may be purchasedby a physician or health care provider for administration at a clinic orhospital.

The computer system 300 illustrated in FIG. 3 may be understood as alogical apparatus that can read instructions from media 311 and/or anetwork port 305, which can optionally be connected to server 309 havingfixed media 312. The system, such as shown in FIG. 3 can include a CPU301, disk drives 303, optional input devices such as keyboard 315 and/ormouse 316 and optional monitor 307. Data communication can be achievedthrough the indicated communication medium to a server at a local or aremote location. The communication medium can include any means oftransmitting and/or receiving data. For example, the communicationmedium can be a network connection, a wireless connection or an internetconnection. Such a connection can provide for communication over theWorld Wide Web. It is envisioned that data relating to the presentdisclosure can be transmitted over such networks or connections forreception and/or review by a party 322 as illustrated in FIG. 3.

EXAMPLES

The following examples are given for the purpose of illustrating variousembodiments of the disclosure and are not meant to limit the presentdisclosure in any fashion. The present examples; along with the methodsdescribed herein are presently representative of preferred embodiments;are exemplary; and are not intended as limitations on the scope of thedisclosure. Changes therein and other uses which are encompassed withinthe spirit of the disclosure as defined by the scope of the claims willoccur to those skilled in the art.

Example 1: Preparation of from about 0.4 Parts to about 0.6 PartsPovidone Iodine USP, 12.0 Parts to about 18.0 Parts Ethyl Pyruvate, and13.6 Parts to about 20.4 Parts Salicylic Acid in 100 Parts of thePharmaceutically Effective Composition for Treatment of Infection

The pharmaceutically effective composition includes from about 0.4 partsto about 0.6 parts povidone iodine USP, 12.0 parts to about 18.0 partsethyl pyruvate, and 13.6 parts to about 20.4 parts salicylic acid USP in100 parts of the pharmaceutically effective composition for treatment ofinfection. The components/compositions are provided in Table 1 thatfollows.

TABLE 1 Unit/Batch Composition Amount/ Per Ingredient 100 ml Batch ^(a)Percent Isopropyl Alcohol ^(b) 26.6-40.8 ml 0.266-0.408 ml 26.6-40.8%2-(2-Ethoxyethoxy) ethanol NF 20.0-30.0 ml 0.20-0.3  ml 20-30%(Transcutol P) ^(c) Ethyl pyruvate ^(d) 12.0-18.0 ml 0.12-0.18 ml12.0-18.0% Propylene Glycol 4.2-5.8 gm 0.042-0.058 g 4.2-5.8% (1,2dihydroxy Propane) ^(e) Glycerin USP ^(f) 0.8-1.2 ml 0.008-0.012 ml0.8-1.2% Salicylic Acid USP ^(g) 13.6-20.4 gm 0.136-0.20  g 13.6-20.4%Butylated Hydroxytoluene NF 0.32-0.48 gm 0.032-0.048 g 3.2-4.8% (BHT)^(h) Hydroxypropylcellulose NF 1500 1.44-2.16 gm 0.0144-0.0216 g1.44-2.16% CPS Povidone Iodine USP 0.4-0.6 gm 0.004-0.006 g 0.4-0.6%Triethanolamine 0.24-0.36 gm 0.0024-0.0036 g 0.24-0.36% ^(a) Slightoverages of the drug substances may be used as required to offset lossesduring manufacture. ^(b) Available from Nexeo Solutions, Rensselaer, NY12144. ^(c) Available from Gattefosse, Paramus, NJ 07652. ^(d) Availablefrom Spectrum Fine Chemcals, New Brunswick, NJ 08901-3605. ^(e)Available from Kraft Chemical, Melrose Park, IL 60160. ^(f) Availablefrom Jeen Chemical, Fairfield, NJ 07004. ^(g-i) Available from SpectrumFine Chemcals, New Brunswick, NJ 08901-3605. ^(j) Available from AstroChemcals, Springfield, MA 01104.

A pharmaceutically effective composition, in 100 parts, having fromabout 0.4 parts to about 0.6 parts povidone iodine USP, 12.0 parts toabout 18.0 parts ethyl pyruvate, and 13.6 parts to about 20.4 partssalicylic acid USP may be formulated by mixing the components listed inTable 1, supra, according to the following general method 200.

In step 1 of the method 200, isopropyl alcohol, 2-(2-ethoxyethoxy)ethanol NF (Transcutol P), ethyl pyruvate, propylene glycol (1,2dihydroxy Propane), Glycerin USP, salicylic acid USP, and butylatedhydroxy toluene (BHT NF) are incrementally added with mixing in a highshear mixer for 30 minutes, forming a solution. In step 2 of the method200, hydroxypropyl cellulose NF (HPC) is incrementally added to thesolution of step 1 with continued mixing, resulting in a thickenedmixture. In step 3 of the method 200, povidone Iodine USP andtriethanolamine are incrementally added to the thickened mixture of step2 with mixing, forming a thickened mixture that may be topically appliedto an infection of the skin, e.g., a wart.

The pharmaceutically effective composition having, in 100 parts, fromabout 0.4 parts to about 0.6 parts povidone iodine USP, 12.0 parts toabout 18.0 parts ethyl pyruvate, and 13.6 parts to about 20.4 partssalicylic acid USP and formulated by mixing the components listed inTable 1, supra, according to the general method 200, was topicallyapplied to a total of 12 patients (n=12) having documented warts. Theseresistant wart patients had been previously treated with at least onetherapy. Treatment in accordance with the method 100 resulted in ahigher cure rate than would be achieved if the infection were treated bytopically applying a control composition having only the keratolytic andbalance being the pharmaceutically acceptable excipient.¹ Patientsranged in age from 14 to 66 years old. The pharmaceutically effectivecomposition of the present disclosure was exclusively used by patientsto treat their verrucae of the lower extremity, including: the knee,lower leg, ankle, foot, and toes. No other treatments were provided.Biopsies were performed on most patients and confirmed verruca in allpatients that were biopsied.

During the course of the study period, patients were instructed to usethe pharmaceutically effective composition of the present disclosure, inthe morning after a shower with a Band-Aid and at night before bedwithout occlusion. The patient was further instructed to self-debridedaily with a file or pumice stone before application, wash and dry thearea well before application, and change socks and shoes twice daily.The patient was seen every 2 weeks for reevaluation, debridement, andapplication in the office.

Following completion of the study and resolution of the warts, thepatient was seen 2 weeks post-clearing for reevaluation, 4 weekspost-clearing for an additional check and at 8 weeks post-clearing for afinal reevaluation confirming complete resolution before discharge.

Of the 12 patients treated with the pharmaceutically effectivecomposition of the present disclosure, in our practice, all wartsresolved, with most in 2-6 weeks. Of particular note was a verydifficult case that involved 2 large mosaic verruca measuring 2 cm×3 cmon the plantar medial hallux and 4 cm×5 cm plantar heel respectivelythat were resistant to multiple therapies for 14 months. Previoustreatments by 2 podiatrists and a dermatologist were unsuccessful usingoral Vitamin A, oral cimetidine, a variety of topicals, laser and Candininjections. Biopsy confirmed diagnosis of verruca. After 20 weeks ofbeing treated with the pharmaceutically effective composition of thepresent disclosure all lesions resolved with no reoccurrence.

We note of particular importance when using the pharmaceuticallyeffective composition of the present disclosure was ensuring a lag timebetween showering and application and a lag time between application andputting on socks and shoe-gear. In addition we note that it is importantto emphasize to patients to rub the pharmaceutically effectivecomposition of the present disclosure well into and on the treatedlesion and letting it dry before proceeding with daily activities.

Alternatively, a pharmaceutically effective composition, in 100 parts,for treating skin infections may be prepared according to the method200, advantageously having in 100 parts of the composition, 0-99 partsof a pharmaceutically acceptable excipient, 49.9-10 parts of akeratolytic, 50-5 parts ethyl pyruvate, and 19-0.1 parts povidoneiodine. The components/compositions are provided in Table 2, as follows.

TABLE 2 Unit/Batch Composition Amount/ Per Ingredient 100 ml Batch ^(a)Percent Isopropyl Alcohol ^(b) 20.0-30.0 ml 0.2-0.3 ml 20.0-30.0%2-(2-Ethoxyethoxy) ethanol NF 20.0-30.0 ml 0.20-0.3  ml 20-30%(Transcutol P) ^(c) Ethyl pyruvate ^(d) 12.0-18.0 ml 0.12-0.18 ml12.0-18.0% Propylene Glycol 1.6-2.4 gm 0.016-0.024 g 1.6-2.4% (1,2dihydroxy Propane) ^(e) Glycerin USP ^(f) 0.8-1.2 ml 0.008-0.012 ml0.8-1.2% Salicylic Acid USP ^(g) 23.2-28.8 gm 0.232-0.288 g 23.2-28.8%Butylated Hydroxytoluene NF 0.32-0.48 gm 0.032-0.048 g 3.2-4.8% (BHT)^(h) Hydroxypropylcellulose NF 1500 1.44-2.16 gm 0.0144-0.0216 g1.44-2.16% CPS Povidone Iodine USP 0.4-0.6 gm 0.004-0.006 g 0.4-0.6%Triethanolamine 0.24-0.36 gm 0.0024-0.0036 g 0.24-0.36% ^(a) Slightoverages of the drug substances may be used as required to offset lossesduring manufacture. ^(b) Available from Nexeo Solutions, Rensselaer, NY12144. ^(c) Available from Gattefosse, Paramus, NJ 07652. ^(d) Availablefrom Spectrum Fine Chemcals, New Brunswick, NJ 08901-3605. ^(e)Available from Kraft Chemical, Melrose Park, IL 60160. f Available fromJeen Chemical, Fairfield, NJ 07004. ^(g-i) Available from Spectrum FineChemcals, New Brunswick, NJ 08901-3605. ^(j) Available from AstroChemcals, Springfield, MA 01104.

FIG. 2 depicts results from topical treatment of resistant wart patientsin accord with the method 100. The chart of FIG. 2 illustrates percentcure of warts (verrucae) in accordance with the method 100.Approximately 80% of resistant warts cleared in just 2-6 week.Approximately 90.9% of the warts in the patients cleared; n=11, in 4-6weeks.

The foregoing description of the embodiments of this disclosure has beenpresented for purposes of illustration and description. It is notintended to be exhaustive or to limit the disclosure to the precise formdisclosed, and obviously, many modifications and variations arepossible. Such modifications and variations that may be apparent to aperson skilled in the art are intended to be included within the scopeof this disclosure as defined by the accompanying claims.

Example 3: Liquid Formulation

A composition of the current disclosure may be formulated as a liquidfor topical administration with the composition listed in Table 3.

TABLE 3 Liquid formulation Ingredient Quantity Sodium chloride 0.9 g/100mL Salicylic acid  13 g/100 mL Ethyl pyruvate 12 mL/100 mL Polyvinylpyrrolidone-iodine 0.4 g/100 mL Methylparaben 1 mg/mL Compoundof Formula I 0.5 g/100 mL Water Up to 100 mL

Example 4: Paste Formulation

A composition of the current disclosure may be formulated as a paste fortopical administration with the composition listed in Table 4.

TABLE 4 Paste formulation Ingredient Quantity (mol %) Zinc oxide 25Starch 25 Salicylic acid 20 Ethyl pyruvate 12Polyvinylpyrrolidone-iodine 0.2 Calamine 5 White petroleum 12.8

Example 5: Paste Formulation

A composition of the current disclosure may be formulated as a paste fortopical administration with the composition listed in Table 5.

TABLE 5 Paste formulation Ingredient Quantity Zinc oxide 20 g Starch 20g Salicylic acid 13.6 g Ethyl pyruvate 12 mL Polyvinylpyrrolidone-iodine0.4 g Calamine 3 g White petroleum 10 g

Example 6: Ointment Formulation

A composition of the current disclosure may be formulated as an ointmentfor topical administration with the composition listed in Table 6.

TABLE 6 Ointment formulation Ingredient Quantity (mol %) Salicylic acid28 Ethyl pyruvate 12 Polyvinylpyrrolidone-iodine 0.6 White wax 5 Whitepetroleum 54.4

Example 7: Ointment Formulation

A composition of the current disclosure may be formulated as an ointmentfor topical administration with the composition listed in Table 7.

TABLE 7 Ointment formulation Ingredient Quantity (weight %) Salicylicacid 28.8 Ethyl pyruvate 20 Polyvinylpyrrolidone-iodine 0.6 White wax 5White petroleum 45.6

Example 8: Cream Formulation

A composition of the current disclosure may be formulated as a cream fortopical administration with the composition listed in Table 8.

TABLE 8 Cream formulation Ingredient Quantity (weight %) Almond oil 35White wax 20 Salicylic acid 28 Ethyl pyruvate 12Polyvinylpyrrolidone-iodine 0.2 Rose water 2 Rose oil 0.02 Water 2.78

Example 9: Gel Formulation

A composition of the current disclosure may be formulated as a gel fortopical administration with the composition listed in Table 9.

TABLE 9 Gel formulation Ingredient Quantity (mol %) Salicylic acid 28Propylene glycol 20 Ethyl pyruvate 12 Polyvinylpyrrolidone-iodine 0.2Methylparaben 0.015 Purified water 39.785

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the disclosure. It should beunderstood that various alternatives to the embodiments of thedisclosure described herein may be employed in practicing thedisclosure.

What is claimed is:
 1. A method for treating a viral wart in a subjectin need thereof, comprising administering to the subject atherapeutically effective amount of a pharmaceutical composition,wherein the pharmaceutical composition comprises: a) about 15 weight %to about 30 weight % of a keratolytic agent comprising salicylic acid,an ester thereof, or a salt thereof, wherein the weight % of thekeratolytic agent is based on a total weight % of the composition; b)about 10 weight % to about 20 weight % of a molecule comprising apyruvate group that is methyl pyruvate, ethyl pyruvate, or propylpyruvate, wherein the weight % of the molecule comprising the pyruvategroup is based on a total weight % of the composition; c) about 0.1weight % to about 1 weight % of polyvinylpyrrolidone-iodine, wherein theweight % of the polyvinylpyrrolidone-iodine is based on a total weight %of the composition; and d) at least 35 weight % of an organic solventcomprising one or more alcohols, wherein the pharmaceutical compositionresolves the viral wart in the subject within 6 weeks following theadministration.
 2. The method of claim 1, wherein the keratolytic agentfurther comprises pyruvic acid, chloroacetic acid, trichloroacetic acid,menthol, acetic acid, ascorbic acid, pantothenic acid, lactic acid, or asalt of any of the above.
 3. The method of claim 1, wherein thepharmaceutical composition comprises about 17 weight % of thekeratolytic agent.
 4. The method of claim 1, wherein the moleculecomprising the pyruvate group is the ethyl pyruvate.
 5. The method ofclaim 1, wherein the pharmaceutical composition comprises about 15weight % of the molecule comprising the pyruvate group.
 6. The method ofclaim 1, wherein the pharmaceutical composition comprises about 0.5weight % of the polyvinylpyrrolidone-iodine.
 7. The method of claim 1,wherein the pharmaceutical composition comprises at least about 40weight % of the organic solvent.
 8. The method of claim 1, wherein thepharmaceutical composition further comprises a pharmaceuticallyacceptable excipient.
 9. The method of claim 8, wherein the excipientcomprises glycerin, propylene glycol, transcutol, triethanolamine, orhydroxypropyl cellulose.
 10. The method of claim 1, wherein thepharmaceutical composition further comprises transcutol.
 11. The methodof claim 1, wherein the pharmaceutical composition further comprisesnitrocellulose.
 12. The method of claim 1, wherein the pharmaceuticalcomposition further comprises polyethylene glycol.
 13. The method ofclaim 1, wherein the pharmaceutical composition further comprisesbutylated hydroxy toluene.
 14. The method of claim 1, wherein thepharmaceutical composition is formulated for topical administration. 15.The method of claim 1, wherein the subject is a human.